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1. 发明授权

US07545491B2 Method and apparatus for sorting cells 有权
标题翻译：用于分选细胞的方法和装置
公开(公告)号：US07545491B2
公开(公告)日：2009-06-09
申请号：US12071020
申请日：2008-02-14
申请人： Daniel Mueth , Amy Anderson , Christopher Knutson , Joseph Plewa
发明人： Daniel Mueth , Amy Anderson , Christopher Knutson , Joseph Plewa
IPC分类号： G01N21/47 , G01N21/01
CPC分类号： G01N21/6428 , C12M47/04 , G01N15/1404 , G01N15/1459 , G01N2015/1409 , G01N2015/1411 , G01N2015/149
摘要： Apparatus for sorting and orienting sperm cells has a pair or walls in confronting relationship forming a flow chamber having inlet, a downstream outlet, and intermediate detector region. The inlet receives first and second spaced apart streams of input fluid and a third stream of sample fluid containing the cells to be sorted. The first and second streams have respective flow rates relative to third stream, such that the third stream is constricted forming a relatively narrow sample stream, so that the cells are oriented parallel to the walls. A detector detects desired cells and a sorter downstream of the detector for sorting the desired cells from the stream.
摘要翻译：用于分选和定向精子细胞的装置具有一对或多个相对关系的壁，形成具有入口，下游出口和中间检测器区域的流动室。入口接收第一和第二间隔开的输入流体流和含有待分选细胞的第三流样品流体。第一和第二流相对于第三流具有相应的流速，使得第三流收缩形成相对窄的样品流，使得电池平行于壁取向。检测器检测期望的细胞和检测器下游的分选器，用于从流中分选所需的细胞。

2. 发明申请

US20060170912A1 Method and apparatus for sorting cells 有权
标题翻译：用于分选细胞的方法和装置
公开(公告)号：US20060170912A1
公开(公告)日：2006-08-03
申请号：US11046896
申请日：2005-02-01
申请人： Daniel Mueth , Amy Anderson , Christopher Knutson , Joseph Plewa
发明人： Daniel Mueth , Amy Anderson , Christopher Knutson , Joseph Plewa
IPC分类号： G01N21/01
CPC分类号： G01N21/6428 , C12M47/04 , G01N15/1404 , G01N15/1459 , G01N2015/1409 , G01N2015/1411 , G01N2015/149
摘要： Apparatus for sorting and orienting sperm cells has a pair or walls in confronting relationship forming a flow chamber having inlet, a downstream outlet, and intermediate detector region. The inlet receives first and second spaced apart streams of input fluid and a third stream of sample fluid containing the cells to be sorted. The first and second streams have respective flow rates relative to third stream, such that the third stream is constricted forming a relatively narrow sample stream, so that the cells are oriented parallel to the walls. A detector detect desired cells and a sorter downstream of the detector for sorting the desired cells from the stream.
摘要翻译：用于分选和定向精子细胞的装置具有一对或多个相对关系的壁，形成具有入口，下游出口和中间检测器区域的流动室。入口接收第一和第二间隔开的输入流体流和含有待分选细胞的第三流样品流体。第一和第二流相对于第三流具有相应的流速，使得第三流收缩形成相对窄的样品流，使得电池平行于壁取向。检测器检测期望的细胞和检测器下游的分选器，用于从流中分选所需的细胞。

3. 发明申请

US20060172315A1 Methods for staining cells for identification and sorting 审中-公开
标题翻译：染色细胞进行鉴定和分选的方法
公开(公告)号：US20060172315A1
公开(公告)日：2006-08-03
申请号：US11048101
申请日：2005-02-01
申请人： Amy Anderson , Christopher Knutson , Daniel Mueth , Joseph Plewa , Evan Tanner
发明人： Amy Anderson , Christopher Knutson , Daniel Mueth , Joseph Plewa , Evan Tanner
IPC分类号： C12Q1/68 , G01N33/48
CPC分类号： C12N5/0612 , A61D19/04 , B82Y5/00 , B82Y10/00 , C12N5/061 , G01N1/30 , G01N15/14 , G01N15/1425 , G01N21/6428 , G01N33/5005 , G01N33/689 , G01N2015/0065 , G01N2015/1006 , G01N2015/1081 , G01N2015/149 , G01N2021/6439
摘要： The present invention provides novel methods of cell staining, such as bovine sperm, using electroporation or osmolality treatments at viability-enhancing temperatures. Furthermore, methods of highly efficient cell sorting that are especially suitable in sorting bovine sperm using novel cell staining procedures are also provided.
摘要翻译：本发明提供新的细胞染色方法，例如牛精子，在活力增强温度下使用电穿孔或渗透压浓度处理。此外，还提供了使用新型细胞染色方法特别适用于分选牛精子的高效细胞分选方法。

4. 发明申请

US20080285099A1 Method and apparatus for forming multi-dimensional colloidal structures using holographic optical tweezers 审中-公开
标题翻译：使用全息光学镊子形成多维胶体结构的方法和装置
公开(公告)号：US20080285099A1
公开(公告)日：2008-11-20
申请号：US11484598
申请日：2006-07-12
申请人： Christopher Knutson , Joseph Plewa
发明人： Christopher Knutson , Joseph Plewa
IPC分类号： G02B5/32
CPC分类号： B01L3/502761 , B01L2400/0454 , G03H1/0005 , G03H2001/0077
摘要： Holographic optical tweezers are used to position charge stabilized colloidal particles within a flow cell. Once the particles are positioned, fixation is accomplished by pumping an electrolyte solution or pH adjusted solution (or a combination of the two) into the sample cell. In the former, the Debye length is reduced and aggregation caused by the van der Waals attraction takes place. In the latter, the surface charge density of the suspension is reduced and aggregation caused by the van der Waals attraction takes place. This technique can be applied multiple times, and allows for the formation of two and three dimensional structures composed of multi-colloid types to be formed on or away from a substrate. The technique relies upon forces acting on virtually all colloidal dispersions making it applicable to a wide variety of colloid types and compositions, such as formation of photonic crystals, colloidal electronics, and bioengineered materials.
摘要翻译：全息光学镊子用于将电荷稳定的胶体颗粒定位在流动池内。一旦颗粒定位，通过将电解质溶液或pH调节的溶液（或两者的组合）泵送到样品池中来实现固定。在前者中，德拜长度减小，范德华力引起的聚集发生。在后者中，悬浮液的表面电荷密度降低，并且由范德华力引起的聚集发生。该技术可以多次施加，并且允许形成由多个胶体类型组成的二维和三维结构形成在基底上或离开基底。该技术依赖于几乎所有胶体分散体上的作用力，使其适用于各种胶体类型和组合物，例如形成光子晶体，胶体电子学和生物工程材料。

5. 发明授权

US08169600B2 Surface mapping by optical manipulation of particles in relation to a functionalized surface 有权
标题翻译：通过相对于功能化表面的颗粒的光学操作的表面映射
公开(公告)号：US08169600B2
公开(公告)日：2012-05-01
申请号：US12440949
申请日：2007-09-14
申请人： Christopher Knutson , Crystal Duke , Gary Stacey , Dan Mueth , Evan Tanner , Osman Akcakir , Haojun Fu , Robert Lancelot , Tania Chakrabarty , Kenneth Bradley
发明人： Christopher Knutson , Crystal Duke , Gary Stacey , Dan Mueth , Evan Tanner , Osman Akcakir , Haojun Fu , Robert Lancelot , Tania Chakrabarty , Kenneth Bradley
IPC分类号： G01N33/48
CPC分类号： G01N33/48 , G01N33/54373 , G01N33/80
摘要： Methods and apparatus for analyzing surface properties of particles are provided. A method for analyzing the surface properties of the particle includes a associating a first particle with a first capture zone having a specific binding affinity for a first chemical species, applying an optical force to the first particle, sensing a response of the first particle to the optical force, and using the sensed response to determine the presence, absence or quantity of the first chemical species on the first particle surface. This process may be repeated in parallel to test multiple particles. In addition to directly testing the surface properties of the particles, the method can be used in direct, indirect and competitive assays to determine the presence, absence or quantity of free or immobilized analytes. A fluidic cartridge with capture zones having avidities that are tuned for the use of optical forces is provided. A software routine for performing the method is also provided.
摘要翻译：提供了分析颗粒表面性质的方法和装置。用于分析颗粒的表面性质的方法包括将第一颗粒与对第一化学物质具有特异性结合亲和力的第一捕获区缔合，向第一颗粒施加光学力，感测第一颗粒对第一颗粒的响应并且使用感测到的响应来确定第一颗粒表面上的第一化学物质的存在，不存在或数量。该过程可以并行重复以测试多个颗粒。除了直接测试颗粒的表面性质之外，该方法可用于直接，间接和竞争性测定，以确定游离或固定化分析物的存在，不存在或数量。提供了一种具有捕获区域的流体盒，其具有被调整以用于光学力的空间。还提供了用于执行该方法的软件程序。

6. 发明申请

US20130273571A1 METHOD OF FUNCTIONALIZING HUMAN RED BLOOD CELLS WITH ANTIBODY 审中-公开
标题翻译：用抗体功能化人红血球细胞的方法
公开(公告)号：US20130273571A1
公开(公告)日：2013-10-17
申请号：US13696171
申请日：2011-05-05
申请人： Christopher Knutson , Derek David Doorneweerd
发明人： Christopher Knutson , Derek David Doorneweerd
IPC分类号： G01N33/555
CPC分类号： G01N33/555 , C07K1/22
摘要： The present invention relates to producing more densely functionalized indicator cells which along, with other components, can be used to detect the presence or absence of antibodies or antigens, by using the A, B, AB and MNS antigens which have a greater degree of expression than the conventionally used D antigen to label the indicator cells with IgG. The present antigen systems have levels of expression that approach one million antigens per cell, which is in great contrast to the conventional D antigen sites of about 10,000-30,000 antigens per cell. This marked increase in the antigen systems level of expression could produce a boost in the kinetics and the magnitude of the binding of the indicator cell to the solid phase, which improves assay performance.
摘要翻译：本发明涉及生产更致密功能化的指示细胞，通过使用具有更高表达程度的A，B，AB和MNS抗原，其与其它组分一起可用于检测抗体或抗原的存在或不存在比常规使用的D抗原用IgG标记指示细胞。目前的抗原系统具有每个细胞接近100万个抗原的表达水平，这与每个细胞约10,000-30,000个抗原的常规D抗原位点形成鲜明的对比。抗原系统的这种显着增加的表达水平可以提高动力学和指示细胞与固相结合的程度，从而提高了测定性能。

7. 发明授权

US09176152B2 Methods and apparatuses for detection of positional freedom of particles in biological and chemical analyses and applications in immunodiagnostics 有权
标题翻译：用于检测生物和化学分析中颗粒的位置自由度的方法和装置以及在免疫诊断中的应用
公开(公告)号：US09176152B2
公开(公告)日：2015-11-03
申请号：US13699519
申请日：2011-05-25
申请人： Christopher Knutson , Osman Akcakir , Haojun Fu
发明人： Christopher Knutson , Osman Akcakir , Haojun Fu
IPC分类号： G01N33/80 , G01N33/50 , G01N33/53 , G01N33/543 , C40B30/04 , G01N15/02 , G01N15/14 , G06F19/10 , G01N21/45
CPC分类号： G01N33/80 , C40B30/04 , G01N15/0211 , G01N15/1463 , G01N21/453 , G01N33/5029 , G01N33/53 , G01N33/54313 , G01N2015/0216 , G01N2015/1497 , G06F19/10
摘要： The present invention relates to methods and apparatuses for the detection of positional freedom of particles used in biological, biochemical, physical, biophysical, and chemical analyses. In particular, the present invention relates to methods and apparatuses which can detect and characterize a population of particles/cells based upon their detected mobility. In one embodiment consistent with the invention, detection of certain cells is based on differences detected in populations of cells that bind to a substrate and those that exhibit weaker binding forces. Initially, cells are settled on the substrate, and in the presence of gravitational, natural thermodynamic pressure fluctuations, and other random or applied forces, some of the particles may exhibit translational movement. Particle movement is detected, and measurements are computed, according to the methods and apparatuses of the present invention, to determine the binding of specific analytes.
摘要翻译：本发明涉及用于检测生物，生化，物理，生物物理和化学分析中使用的颗粒的位置自由度的方法和装置。特别地，本发明涉及可以基于其检测到的移动性来检测和表征粒子/细胞群体的方法和装置。在与本发明一致的一个实施方案中，某些细胞的检测基于在与底物结合的细胞群体中检测到的差异以及显示较弱结合力的细胞的差异。最初，细胞沉积在基底上，并且在重力，天然热力学压力波动和其它随机或施加的力的存在下，一些颗粒可能表现出平移运动。检测到颗粒运动，并且根据本发明的方法和装置计算测量值，以确定特定分析物的结合。

8. 发明申请

US20130274119A1 METHODS AND APPARATUSES FOR DETECTION OF POSITIONAL FREEDOM OF PARTICLES IN BIOLOGICAL AND CHEMICAL ANALYSES AND APPLICATIONS IN IMMUNODIAGNOSTICS 有权
标题翻译：用于检测生物和化学分析中颗粒的位置自由的方法和装置及其在免疫组织化学中的应用
公开(公告)号：US20130274119A1
公开(公告)日：2013-10-17
申请号：US13699519
申请日：2011-05-25
申请人： Christopher Knutson , Osman Akcakir , Haojun Fu
发明人： Christopher Knutson , Osman Akcakir , Haojun Fu
IPC分类号： G01N33/80
CPC分类号： G01N33/80 , C40B30/04 , G01N15/0211 , G01N15/1463 , G01N21/453 , G01N33/5029 , G01N33/53 , G01N33/54313 , G01N2015/0216 , G01N2015/1497 , G06F19/10
摘要： The present invention relates to methods and apparatuses for the detection of positional freedom of particles used in biological, biochemical, physical, biophysical, and chemical analyses. In particular, the present invention relates to methods and apparatuses which can detect and characterize a population of particles/cells based upon their detected mobility. In one embodiment consistent with the invention, detection of certain cells is based on differences detected in populations of cells that bind to a substrate and those that exhibit weaker binding forces. Initially, cells are settled on the substrate, and in the presence of gravitational, natural thermodynamic pressure fluctuations, and other random or applied forces, some of the particles may exhibit translational movement. Particle movement is detected, and measurements are computed, according to the methods and apparatuses of the present invention, to determine the binding of specific analytes.
摘要翻译：本发明涉及用于检测生物，生化，物理，生物物理和化学分析中使用的颗粒的位置自由度的方法和装置。特别地，本发明涉及可以基于其检测到的移动性来检测和表征粒子/细胞群体的方法和装置。在与本发明一致的一个实施方案中，某些细胞的检测基于在与底物结合的细胞群体中检测到的差异以及显示较弱结合力的细胞的差异。最初，细胞沉积在基底上，并且在重力，天然热力学压力波动和其它随机或施加的力的存在下，一些颗粒可能表现出平移运动。检测到颗粒运动，并且根据本发明的方法和装置计算测量值，以确定特定分析物的结合。

9. 发明申请

US20110026009A1 Surface Mapping by Optical Manipulation of Particles in Relation to a Functionalized Surface 有权
标题翻译：通过光学操作颗粒与功能化表面的表面贴图
公开(公告)号：US20110026009A1
公开(公告)日：2011-02-03
申请号：US12440949
申请日：2007-09-14
申请人： Christopher Knutson , Crystal Duke , Gary Stacey , Dan Mueth , Evan Tanner , Osman Akcakir , Haojun Fu , Robert Lancelot , Tania Chakrabarty , Kenneth Bradley
发明人： Christopher Knutson , Crystal Duke , Gary Stacey , Dan Mueth , Evan Tanner , Osman Akcakir , Haojun Fu , Robert Lancelot , Tania Chakrabarty , Kenneth Bradley
IPC分类号： G01N33/48 , G01B11/30
CPC分类号： G01N33/48 , G01N33/54373 , G01N33/80
摘要： Methods and apparatus for analyzing surface properties of particles are provided. A method for analyzing the surface properties of the particle includes a associating a first particle with a first capture zone having a specific binding affinity for a first chemical species, applying an optical force to the first particle, sensing a response of the first particle to the optical force, and using the sensed response to determine the presence, absence or quantity of the first chemical species on the first particle surface. This process may be repeated in parallel to test multiple particles. In addition to directly testing the surface properties of the particles, the method can be used in direct, indirect and competitive assays to determine the presence, absence or quantity of free or immobilized analytes. A fluidic cartridge with capture zones having avidities that are tuned for the use of optical forces is provided. A software routine for performing the method is also provided.
摘要翻译：提供了分析颗粒表面性质的方法和装置。用于分析颗粒的表面性质的方法包括将第一颗粒与对第一化学物质具有特异性结合亲和力的第一捕获区缔合，向第一颗粒施加光学力，感测第一颗粒对第一颗粒的响应并且使用感测到的响应来确定第一颗粒表面上的第一化学物质的存在，不存在或数量。该过程可以并行重复以测试多个颗粒。除了直接测试颗粒的表面性质之外，该方法可用于直接，间接和竞争性测定，以确定游离或固定化分析物的存在，不存在或数量。提供了一种具有捕获区域的流体盒，其具有被调整以用于光学力的空间。还提供了用于执行该方法的软件程序。

10. 发明申请

US20080145627A1 Nanoscale masking and printing using patterned substrates 审中-公开
标题翻译：使用图案化衬底的纳米级掩模和印刷
公开(公告)号：US20080145627A1
公开(公告)日：2008-06-19
申请号：US11822215
申请日：2007-07-03
申请人： Christopher Knutson
发明人： Christopher Knutson
IPC分类号： B32B3/08 , B05D5/00 , B32B33/00
CPC分类号： B01J19/0046 , B01J2219/00382 , B01J2219/005 , B01J2219/00527 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/00617 , B01J2219/00648 , B01J2219/00659 , B01J2219/00677 , B01J2219/00722 , B01J2219/00725 , B01J2219/00745 , Y10T428/24893 , Y10T428/2982
摘要： Nanoscale masking using particles patterned on a substrate include assembling particles into a pattern on a first substrate; contacting the particles with a second substrate; adding blocking molecules while the particles are in contact, such that blocking molecules bind to portions of the second substrate not in contact with the particles; and separating the substrates, yielding a functionalized substrate having blocking molecules bound thereto. Nanoscale printing methods include assembling particles into a desired pattern on a first substrate; contacting a print material with the particles such that at least a portion of the print material binds to the particles on the first substrate; removing the first substrate having particles thereon from unbound print material; contacting the particles having print material bound thereto with a second substrate such that at least a portion of the print material binds to the second substrate; and separating the substrates, yielding a printed substrate.
摘要翻译：使用在基板上图案化的颗粒的纳米级掩模包括将颗粒组装成第一基板上的图案; 使颗粒与第二底物接触; 在颗粒接触的同时加入阻挡分子，使得阻挡分子与不与颗粒接触的第二基底的部分结合; 并分离底物，产生具有与其结合的阻断分子的官能化底物。纳米级印刷方法包括在第一基底上将颗粒组装成所需图案; 使打印材料与颗粒接触，使得至少一部分印刷材料与第一基底上的颗粒结合; 从未结合的印刷材料中除去其上具有颗粒的第一基板; 使具有与其结合的印刷材料的颗粒与第二基板接触，使得至少一部分印刷材料结合到第二基板; 并分离衬底，产生印刷衬底。

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